Diastereoselective FeCl 3 ·6H 2 O/NaBH 4 Reduction of Oxime Ether for the Synthesis of β-Lactamase Inhibitor Relebactam
Relebactam, a potent β-lactamase inhibitor, in combination with Primaxin is an FDA-approved (Recarbrio) treatment for serious and antibiotic-resistant bacterial infections. An efficient synthesis of key chiral piperidine intermediate suitable for large-scale preparation of relebactam is described. T...
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| Veröffentlicht in: | Journal of organic chemistry 2020-01, Vol.85 (2), p.994-1000 |
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| container_title | Journal of organic chemistry |
| container_volume | 85 |
| creator | Chung, John Y L Meng, Dongfang Shevlin, Michael Gudipati, Venugopal Chen, Qinghao Liu, Yizhou Lam, Yu-Hong Dumas, Aaron Scott, Jeremy Tu, Qiang Xu, Feng |
| description | Relebactam, a potent β-lactamase inhibitor, in combination with Primaxin is an FDA-approved (Recarbrio) treatment for serious and antibiotic-resistant bacterial infections. An efficient synthesis of key chiral piperidine intermediate
suitable for large-scale preparation of relebactam is described. The key steps include a unique highly diastereoselective FeCl
·6H
O/NaBH
reduction of a chiral oxime ether and chemoselective amidation of the resulting unprotected pipecolic acid. Nuclear magnetic resonance studies and density functional theory calculations were carried out on the substrate-Fe(III) complexes, which shed light on diastereoselective reduction. |
| doi_str_mv | 10.1021/acs.joc.9b02948 |
| format | Article |
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suitable for large-scale preparation of relebactam is described. The key steps include a unique highly diastereoselective FeCl
·6H
O/NaBH
reduction of a chiral oxime ether and chemoselective amidation of the resulting unprotected pipecolic acid. Nuclear magnetic resonance studies and density functional theory calculations were carried out on the substrate-Fe(III) complexes, which shed light on diastereoselective reduction.</description><identifier>ISSN: 0022-3263</identifier><identifier>EISSN: 1520-6904</identifier><identifier>DOI: 10.1021/acs.joc.9b02948</identifier><identifier>PMID: 31850754</identifier><language>eng</language><publisher>United States</publisher><subject>Azabicyclo Compounds - chemical synthesis ; Azabicyclo Compounds - chemistry ; Azabicyclo Compounds - pharmacology ; beta-Lactamase Inhibitors - chemical synthesis ; beta-Lactamase Inhibitors - pharmacology ; Borohydrides - chemistry ; Chlorides - chemistry ; Ethers - chemistry ; Ferric Compounds - chemistry ; Molecular Structure ; Oxidation-Reduction ; Oximes - chemistry ; Spectrum Analysis - methods ; Stereoisomerism ; Water - chemistry</subject><ispartof>Journal of organic chemistry, 2020-01, Vol.85 (2), p.994-1000</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c1094-5e3522509a589c19ee70e0992c23f80144e11ec1e634487089badcd4046b52143</citedby><cites>FETCH-LOGICAL-c1094-5e3522509a589c19ee70e0992c23f80144e11ec1e634487089badcd4046b52143</cites><orcidid>0000-0003-1949-324X ; 0000-0001-6094-5549 ; 0000-0002-3510-8228 ; 0000-0002-4946-1487 ; 0000-0003-2566-5095</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,2752,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31850754$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chung, John Y L</creatorcontrib><creatorcontrib>Meng, Dongfang</creatorcontrib><creatorcontrib>Shevlin, Michael</creatorcontrib><creatorcontrib>Gudipati, Venugopal</creatorcontrib><creatorcontrib>Chen, Qinghao</creatorcontrib><creatorcontrib>Liu, Yizhou</creatorcontrib><creatorcontrib>Lam, Yu-Hong</creatorcontrib><creatorcontrib>Dumas, Aaron</creatorcontrib><creatorcontrib>Scott, Jeremy</creatorcontrib><creatorcontrib>Tu, Qiang</creatorcontrib><creatorcontrib>Xu, Feng</creatorcontrib><title>Diastereoselective FeCl 3 ·6H 2 O/NaBH 4 Reduction of Oxime Ether for the Synthesis of β-Lactamase Inhibitor Relebactam</title><title>Journal of organic chemistry</title><addtitle>J Org Chem</addtitle><description>Relebactam, a potent β-lactamase inhibitor, in combination with Primaxin is an FDA-approved (Recarbrio) treatment for serious and antibiotic-resistant bacterial infections. An efficient synthesis of key chiral piperidine intermediate
suitable for large-scale preparation of relebactam is described. The key steps include a unique highly diastereoselective FeCl
·6H
O/NaBH
reduction of a chiral oxime ether and chemoselective amidation of the resulting unprotected pipecolic acid. Nuclear magnetic resonance studies and density functional theory calculations were carried out on the substrate-Fe(III) complexes, which shed light on diastereoselective reduction.</description><subject>Azabicyclo Compounds - chemical synthesis</subject><subject>Azabicyclo Compounds - chemistry</subject><subject>Azabicyclo Compounds - pharmacology</subject><subject>beta-Lactamase Inhibitors - chemical synthesis</subject><subject>beta-Lactamase Inhibitors - pharmacology</subject><subject>Borohydrides - chemistry</subject><subject>Chlorides - chemistry</subject><subject>Ethers - chemistry</subject><subject>Ferric Compounds - chemistry</subject><subject>Molecular Structure</subject><subject>Oxidation-Reduction</subject><subject>Oximes - chemistry</subject><subject>Spectrum Analysis - methods</subject><subject>Stereoisomerism</subject><subject>Water - chemistry</subject><issn>0022-3263</issn><issn>1520-6904</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kM9OwkAQhzdGI4ievZl9gcLsv9I9KoKQEElQz812Ow0llJLdYuC1vHj3AXwmF0Hn8ptMvplJPkJuGXQZcNYz1neXte3qDLiWyRlpM8UhijXIc9IG4DwSPBYtcuX9EkIppS5JS7BEQV_JNtk_lsY36LD2uELblO9IRzhYUUG_PuMx5XTWezYPYyrpHPNtAOo1rQs625UV0mGzQEeL2tHQ0Jf9OoQv_QH4_oimxjamMh7pZL0os7IJ3Dx8yX7n1-SiMCuPN6fskLfR8HUwjqazp8ngfhpZBlpGCoXiXIE2KtGWacQ-IGjNLRdFAkxKZAwtw1hImfQh0ZnJbS5BxpniTIoO6R3vWld777BIN66sjNunDNKDxDRITIPE9CQxbNwdNzbbrML8n_-zJn4ADLNuNQ</recordid><startdate>20200117</startdate><enddate>20200117</enddate><creator>Chung, John Y L</creator><creator>Meng, Dongfang</creator><creator>Shevlin, Michael</creator><creator>Gudipati, Venugopal</creator><creator>Chen, Qinghao</creator><creator>Liu, Yizhou</creator><creator>Lam, Yu-Hong</creator><creator>Dumas, Aaron</creator><creator>Scott, Jeremy</creator><creator>Tu, Qiang</creator><creator>Xu, Feng</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><orcidid>https://orcid.org/0000-0003-1949-324X</orcidid><orcidid>https://orcid.org/0000-0001-6094-5549</orcidid><orcidid>https://orcid.org/0000-0002-3510-8228</orcidid><orcidid>https://orcid.org/0000-0002-4946-1487</orcidid><orcidid>https://orcid.org/0000-0003-2566-5095</orcidid></search><sort><creationdate>20200117</creationdate><title>Diastereoselective FeCl 3 ·6H 2 O/NaBH 4 Reduction of Oxime Ether for the Synthesis of β-Lactamase Inhibitor Relebactam</title><author>Chung, John Y L ; Meng, Dongfang ; Shevlin, Michael ; Gudipati, Venugopal ; Chen, Qinghao ; Liu, Yizhou ; Lam, Yu-Hong ; Dumas, Aaron ; Scott, Jeremy ; Tu, Qiang ; Xu, Feng</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c1094-5e3522509a589c19ee70e0992c23f80144e11ec1e634487089badcd4046b52143</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Azabicyclo Compounds - chemical synthesis</topic><topic>Azabicyclo Compounds - chemistry</topic><topic>Azabicyclo Compounds - pharmacology</topic><topic>beta-Lactamase Inhibitors - chemical synthesis</topic><topic>beta-Lactamase Inhibitors - pharmacology</topic><topic>Borohydrides - chemistry</topic><topic>Chlorides - chemistry</topic><topic>Ethers - chemistry</topic><topic>Ferric Compounds - chemistry</topic><topic>Molecular Structure</topic><topic>Oxidation-Reduction</topic><topic>Oximes - chemistry</topic><topic>Spectrum Analysis - methods</topic><topic>Stereoisomerism</topic><topic>Water - chemistry</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chung, John Y L</creatorcontrib><creatorcontrib>Meng, Dongfang</creatorcontrib><creatorcontrib>Shevlin, Michael</creatorcontrib><creatorcontrib>Gudipati, Venugopal</creatorcontrib><creatorcontrib>Chen, Qinghao</creatorcontrib><creatorcontrib>Liu, Yizhou</creatorcontrib><creatorcontrib>Lam, Yu-Hong</creatorcontrib><creatorcontrib>Dumas, Aaron</creatorcontrib><creatorcontrib>Scott, Jeremy</creatorcontrib><creatorcontrib>Tu, Qiang</creatorcontrib><creatorcontrib>Xu, Feng</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Journal of organic chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chung, John Y L</au><au>Meng, Dongfang</au><au>Shevlin, Michael</au><au>Gudipati, Venugopal</au><au>Chen, Qinghao</au><au>Liu, Yizhou</au><au>Lam, Yu-Hong</au><au>Dumas, Aaron</au><au>Scott, Jeremy</au><au>Tu, Qiang</au><au>Xu, Feng</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Diastereoselective FeCl 3 ·6H 2 O/NaBH 4 Reduction of Oxime Ether for the Synthesis of β-Lactamase Inhibitor Relebactam</atitle><jtitle>Journal of organic chemistry</jtitle><addtitle>J Org Chem</addtitle><date>2020-01-17</date><risdate>2020</risdate><volume>85</volume><issue>2</issue><spage>994</spage><epage>1000</epage><pages>994-1000</pages><issn>0022-3263</issn><eissn>1520-6904</eissn><abstract>Relebactam, a potent β-lactamase inhibitor, in combination with Primaxin is an FDA-approved (Recarbrio) treatment for serious and antibiotic-resistant bacterial infections. An efficient synthesis of key chiral piperidine intermediate
suitable for large-scale preparation of relebactam is described. The key steps include a unique highly diastereoselective FeCl
·6H
O/NaBH
reduction of a chiral oxime ether and chemoselective amidation of the resulting unprotected pipecolic acid. Nuclear magnetic resonance studies and density functional theory calculations were carried out on the substrate-Fe(III) complexes, which shed light on diastereoselective reduction.</abstract><cop>United States</cop><pmid>31850754</pmid><doi>10.1021/acs.joc.9b02948</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0003-1949-324X</orcidid><orcidid>https://orcid.org/0000-0001-6094-5549</orcidid><orcidid>https://orcid.org/0000-0002-3510-8228</orcidid><orcidid>https://orcid.org/0000-0002-4946-1487</orcidid><orcidid>https://orcid.org/0000-0003-2566-5095</orcidid></addata></record> |
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| language | eng |
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| source | MEDLINE; American Chemical Society Journals |
| subjects | Azabicyclo Compounds - chemical synthesis Azabicyclo Compounds - chemistry Azabicyclo Compounds - pharmacology beta-Lactamase Inhibitors - chemical synthesis beta-Lactamase Inhibitors - pharmacology Borohydrides - chemistry Chlorides - chemistry Ethers - chemistry Ferric Compounds - chemistry Molecular Structure Oxidation-Reduction Oximes - chemistry Spectrum Analysis - methods Stereoisomerism Water - chemistry |
| title | Diastereoselective FeCl 3 ·6H 2 O/NaBH 4 Reduction of Oxime Ether for the Synthesis of β-Lactamase Inhibitor Relebactam |
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